Heart FailurePhase 3SNOWNCT01586442
Comparison of Eplerenone Versus Spironolactone in Heart Failure Patients With Glucose Intolerance or Type 2 Diabetes
A Phase 3 study testing Eplerenone and Spironolactone in people with Heart Failure and Type 2 Diabetes, run by Montreal Heart Institute at 1 site in Canada.
Trial summary
In this proposal,the investigators will examine whether the selectivity of eplerenone for the MR will translate into a better glucose and metabolic profile compare to spironolactone in patients with HF with glucose intolerance or type 2 diabetes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Type 2 Diabetes, Glucose Intolerance
- What is being tested?
- Eplerenone and Spironolactone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2012to 29 Jul 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female at least 18 years old.
- Symptomatic HF corresponding to NYHA class II-IV symptoms for at least 4 weeks prior randomization.
- A diagnosis of 1) impaired glucose tolerance described as overnight fasting between blood glucose 5.6 and 6.9 mmol/L on two occasions; or 2) type 2 diabetes defined as overnight fasting between blood glucose of 7.0 mmol/L or more on two occasions; a HbA1c equal to or higher than 6.5% or more on two occasions; or as a history of type II diabetes treated with hypoglycemic agents.
- LVEF equal to or lower than 40% documented by, contrast ventriculography, magnetic resonance imaging, radionuclide ventriculography or quantitative echocardiography within the previous 12 months if no cardiac event occurred since the measurement of the LVEF. The most recent measurements should be used.
- Treatment with an optimal and stable dose of ACE inhibitor (or ARB) for at least 4 weeks prior to enrolment in the study. In addition, patients should be treated with a stable dose of beta-blockers for at least 4 weeks prior enrolment in the study. Patients incapable to tolerate bisoprolol, carvedilol or metoprolol will be allowed within the trial.
- Informed consent must be obtained before any study specific procedures are performed
Who cannot join
- Current treatment with a combination of an ARB, an ACE or a renin inhibitor.
- Type 1 diabetes
- Known intolerance or allergy to eplerenone or spironolactone, including gynecomastia with spironolactone.
- Estimated GFR < 30 mL/min/1.73 m2 as calculated using the MDRD equation (Appendix 1).
- Current serum potassium higher than 5.0 mmol/L (higher than 5.0 mEq/L).
- Current symptomatic hypotension and/or systolic B.P. < 90 mmHg.
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- Persistent systolic or diastolic hypertension (systolic > 170 mmHg or diastolic > 100 mmHg despite use of antihypertensive therapy).
- HF secondary to any of the following conditions: hemodynamically significant primary stenotic valvular cardiomyopathy, isolated right sided CHF, non cardiac disease (e.g. uncorrected thyroid disease), pericardial disease, complex congenital heart disease, myocarditis.
- Decompensated heart failure described as hospitalization or I.V. administration of medication in emergency room or heart failure clinic within 4 weeks (ex.: diuretics, inotropes, vasodilatators)
- Current treatment with insulin
- Stroke, acute coronary syndrome, PCI within the last 4 weeks before randomization.
- Cardiac surgery within 3 months.
- Significant liver disease (ALT x 3 times limit of normal).
- Planned cardiac surgery expected to be performed within the next 6 months.
- Previous heart transplant or heart transplant expected to be performed within the next 6 months.
- Presence of any non-cardiac diseases likely to significantly shorten life expectancy to < 1 year.
- Pregnant or lactating women or women of childbearing potential who are not protected from pregnancy by an accepted method of contraception, such as the oral contraceptive pill, an intrauterine device or surgical sterilization (all women of childbearing potential must have a negative pregnancy test before randomization).
- Any condition that in the opinion of the investigator would jeopardize the evaluation on efficacy or safety or be associated with poor adherence to the protocol.
- Treatment with any investigational agent or device within 4 weeks of randomization.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Comparison of the Effects of Selective and Non Selective Mineralocorticoid Antagonism on Glucose Homeostasis and Lipid Profile of Heart Failure Patients With Glucose Intolerance or Type 2 Diabetes.
In this proposal,the investigators will examine whether the selectivity of eplerenone for the MR will translate into a better glucose and metabolic profile compare to spironolactone in patients with HF with glucose intolerance or type 2 diabetes. In addition, the investigators will also compare the impact of these two agents on changes of concentrations of established prognostic biomarkers of neurohormonal activation and extracellular matrix turnover.
- Conditions
- Heart Failure, Type 2 Diabetes, Glucose Intolerance
- Being tested
- Eplerenone, Spironolactone
- Medical subject headings
- Heart Failure, Diabetes Mellitus, Type 2, Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EplerenoneDrug
Also called Inspra
Eplerenone 25mg once daily titrated to 50 mg once daily for 4 months
SpironolactoneDrug
Also called Aldactone
Spironolactone 12,5mg daily titrated to 25mg once daily for 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Active comparator | spironolactone 12.5mg once daily titrated to 25mg once daily Receives: Drug: Spironolactone |
| Eplerenone | Experimental | Eplerenone 25mg once daily titrated to 50mg once daily Receives: Drug: Eplerenone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glycated hemoglobin
Change in glycated hemoglobin
Measured: 4 months
Fasting glucose and lipid profile
Measured: 4 months
Plasma insulin
Measured: 4 months
Cortisol
Measured: 4 months
Adiponectin
Measured: 4 months
NT-proBNP
Measured: 4 months
PIIINP
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2012 (estimated)
- Study startMar 2012
- Primary completionMar 2015
- Study completion29 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montreal Heart Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Michel White, Montreal Heart Institute
- Investigators
- Michel White, MD, Principal investigator, Montreal Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01586442
- Sponsor's protocol ID
- WS1911307
- Acronym
- SNOW
- Status last verified
- Oct 2022
- First submitted
- 24 Apr 2012
- Last updated
- 7 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Korol S, White M, O'Meara E, Tournoux F, Racine N, Ducharme A, Rouleau JL, Liszkowski M, Mansour A, Jutras M, Guertin MC, Bernier M, Lavoie J, Leclair G, Neagoe PE, Chaar D, Sirois MG, de Denus S. A comparison of the effects of selective and non-selective mineralocorticoid antagonism on glucose homeostasis of heart failure patients with glucose intolerance or type II diabetes: A randomized controlled double-blind trial. Am Heart J. 2018 Oct;204:190-195. doi: 10.1016/j.ahj.2018.07.002. Epub 2018 Jul 10.
PubMed 30097164
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparison of the Effects of Selective and Non Selective Mineralocorticoid Antagonism on Glucose Homeostasis and Lipid Profile of Heart Failure Patients With Glucose Intolerance or Type 2 Diabetes.
- ClinicalTrials.gov ID
- NCT01586442
- Acronym / sponsor ID
- SNOW / WS1911307
- Conditions
- Heart Failure, Type 2 Diabetes, Glucose Intolerance
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Montreal Heart InstituteUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Mar 2012
- Primary completion
- Mar 2015 (actual)
- Study completion
- 29 Jul 2018 (actual)
- First posted
- 26 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this proposal,the investigators will examine whether the selectivity of eplerenone for the MR will translate into a better glucose and metabolic profile compare to spironolactone in patients with HF with glucose intolerance or type 2 diabetes. In addition, the investigators will also compare the impact of these two agents on changes of concentrations of established prognostic biomarkers of neurohormonal activation and extracellular matrix turnover.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Active comparator | Drug: Spironolactonespironolactone 12.5mg once daily titrated to 25mg once daily |
| Eplerenone | Experimental | Drug: EplerenoneEplerenone 25mg once daily titrated to 50mg once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female at least 18 years old.
- Symptomatic HF corresponding to NYHA class II-IV symptoms for at least 4 weeks prior randomization.
- A diagnosis of 1) impaired glucose tolerance described as overnight fasting between blood glucose 5.6 and 6.9 mmol/L on two occasions; or 2) type 2 diabetes defined as overnight fasting between blood glucose of 7.0 mmol/L or more on two occasions; a HbA1c equal to or higher than 6.5% or more on two occasions; or as a history of type II diabetes treated with hypoglycemic agents.
- LVEF equal to or lower than 40% documented by, contrast ventriculography, magnetic resonance imaging, radionuclide ventriculography or quantitative echocardiography within the previous 12 months if no cardiac event occurred since the measurement of the LVEF. The most recent measurements should be used.
- Treatment with an optimal and stable dose of ACE inhibitor (or ARB) for at least 4 weeks prior to enrolment in the study. In addition, patients should be treated with a stable dose of beta-blockers for at least 4 weeks prior enrolment in the study. Patients incapable to tolerate bisoprolol, carvedilol or metoprolol will be allowed within the trial.
Key exclusion criteria (19 listed)
- Current treatment with a combination of an ARB, an ACE or a renin inhibitor.
- Type 1 diabetes
- Known intolerance or allergy to eplerenone or spironolactone, including gynecomastia with spironolactone.
- Estimated GFR < 30 mL/min/1.73 m2 as calculated using the MDRD equation (Appendix 1).
- Current serum potassium higher than 5.0 mmol/L (higher than 5.0 mEq/L).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EplerenoneAlso: InspraEplerenone 25mg once daily titrated to 50 mg once daily for 4 months | Drug | Eplerenone |
| SpironolactoneAlso: AldactoneSpironolactone 12,5mg daily titrated to 25mg once daily for 16 weeks | Drug | Spironolactone |
Primary outcome
Glycated hemoglobin
Time frame: 4 months
Change in glycated hemoglobin
Fasting glucose and lipid profile
Time frame: 4 months
Plasma insulin
Time frame: 4 months
Cortisol
Time frame: 4 months
Adiponectin
Time frame: 4 months
NT-proBNP
Time frame: 4 months
PIIINP
Time frame: 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2022.
- Derived from this study: PubMed 30097164Korol S, White M, O'Meara E, Tournoux F, Racine N, Ducharme A, Rouleau JL, Liszkowski M, Mansour A, Jutras M, Guertin MC, Bernier M, Lavoie J, Leclair G, Neagoe PE, Chaar D, Sirois MG, de Denus S. A comparison of the effects of selective and non-selective mineralocorticoid antagonism on glucose homeostasis of heart failure patients with glucose intolerance or type II diabetes: A randomized controlled double-blind trial. Am Heart J. 2018 Oct;204:190-195. doi: 10.1016/j.ahj.2018.07.002. Epub 2018 Jul 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michel White, MD principal investigator
Montreal Heart Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eplerenone and Spironolactone in people with Heart Failure and Type 2 Diabetes, run by Montreal Heart Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glycated hemoglobin (time frame: 4 months). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01586442, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2022.